Combination of organic compounds

Abstract

The present invention relates to a combination of organic compounds, a pharmaceutical composition and a kit of parts comprising said combination of organic compounds and to a method of treatment or prevention of certain conditions or diseases.

1 . A combination comprising 
 (i) an aldosterone receptor antagonist or a pharmaceutically acceptable salt thereof,    (ii) a diuretic or a pharmaceutically acceptable salt thereof, and optionally    (iii) an angiotensin receptor blocker (ARB) or a pharmaceutically acceptable salt thereof.    
   
   
       2 . A combination according to  claim 1 , wherein 
 (i) the aldosterone receptor antagonist is selected from the group consisting of spironolactone or eplerenone;    (ii) the diuretic is selected from the group consisting of bumetanide, ethacrynic acid, furosemide, ethynacrylic acid, mersalyl with theophylline, mercaptomerin sodium, merethoxylline procaine, torsemide, amiloride, spironolactone, triamterene, chlorothalidone, chlorothiazide, quinethazone,hydrochlorothiazide (HCTZ), hydroflumethiazide, methylchlorothiazide, metolazone, and dichlorphenamide; and    (iii) the angiotensin receptor blocker (ARB) is selected from the group consisting of candesartan, eprosartan, irbesartan, losartan, olmesartan, saprisartan, tasosartan, telmisartan, valsartan, E-4177, SC-52458, and ZD8731, or a pharmaceutically acceptable salts thereof.    
   
   
       3 . A combination according to  claim 2 , wherein (i) the aldosterone receptor antagonist is eplerenone; (ii) the diuretic is hydrochlorothiazide; and (iii) the angiotensin receptor blocker (ARB) is valsartan.  
   
   
       4 . A combination according to  claim 3 , wherein valsartan is contained in an amount from about 20 to about 640 mg, eplerenone is contained in an amount from about 10 mg to about 1000 mg, and hydrochlorothiazide is contained in an amount from about 5 mg to about 200 mg.  
   
   
       5 . A combination according to  claim 4 , wherein valsartan is contained in an amount from about 40 to about 320 mg, eplerenone is contained in an amount from about 10 mg to about 100 mg, and hydrochlorothiazide is contained in an amount from about 5 mg to about 25 mg.  
   
   
       6 . Combination according to  claim 1  in the form of a combined preparation or a pharmaceutical composition.  
   
   
       7 . A kit of parts comprising 
 (i) a pharmaceutical composition of an aldosterone receptor antagonist,    (ii) a pharmaceutical composition of a diuretic, and optionally    (iii) a pharmaceutical composition of an angiotensin receptor blocker (ARB) in the form of two or three separate units of the components (i) to (ii) or (i) to (iii).    
   
   
       8 . A kit of parts according to  claim 7 , wherein (i) the aldosterone receptor antagonist is selected from the group consisting of spironolactone or eplerenone; 
 (ii) the diuretic is selected from the group consisting of bumetanide, ethacrynic acid, furosemide, ethynacrylic acid, mersalyl with theophylline, mercaptomerin sodium, merethoxylline procaine, torsemide, amiloride, spironolactone, triamterene, chlorothalidone, chlorothiazide, quinethazone,hydrochlorothiazide (HCTZ), hydroflumethiazide, methylchlorothiazide, metolazone, and dichlorphenamide; and    (iii) the angiotensin receptor blocker (ARB) is selected from the group consisting of candesartan, eprosartan, irbesartan, losartan, olmesartan, saprisartan, tasosartan, telmisartan, valsartan, E-4177, SC-52458, and ZD8731, or a pharmaceutically acceptable salts thereof    
   
   
       9 . A kit of parts according to  claim 8 , wherein (i) the aldosterone receptor antagonist is eplerenone; (ii) the diuretic is hydrochlorothiazide; and (iii) the angiotensin receptor blocker (ARB) is valsartan.  
   
   
       10 . A kit of parts according to  claim 9 , wherein valsartan is contained in an amount from about 20 to about 640 mg, eplerenone is contained in an amount from about 10 mg to about 1000 mg, and hydrochlorothiazide is contained in an amount from about 5 mg to about 200 mg.  
   
   
       11 . A kit of parts according to  claim 10 , wherein valsartan is contained in an amount from about 40 to about 320 mg, eplerenone is contained in an amount from about 10 mg to about 100 mg, and hydrochlorothiazide is contained in an amount from about 5 mg to about 25 mg.  
   
   
       12 . A method of treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke, comprising administering a therapeutically effective amount of combination of 
 (i) an aldosterone receptor antagonist or-a pharmaceutically acceptable salt thereof,    (ii) a diuretic or a pharmaceutically acceptable salt thereof, and optionally    (iii) an angiotensin receptor blocker (ARB) or, where appropriate, a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier to a mammal in need of such treatment.    
   
   
       13 . A commercial package comprising 
 (i) a pharmaceutical composition of an aldosterone receptor antagonist,    (ii) a pharmaceutical composition of a a diuretic , and optionally    (iii) a pharmaceutical composition of a an angiotensin receptor blocker (ARB) in the form of two or three separate units of the components (i) to (ii) or (i) to (iii), together with instructions for simultaneous, separate or sequential use thereof for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke.    
   
   
       14 . A commercial package according to  claim 13 , wherein wherein (i) the aldosterone receptor antagonist is eplerenone; (ii) the diuretic is hydrochlorothiazide; and (iii) the angiotensin receptor blocker (ARB) is valsartan.  
   
   
       15 . A commercial package according to  claim 14 , wherein the angiotensin receptor blocker (ARB) (iii) and the diuretic (ii) are present in the form of Co-DIOVAN®.  
   
   
       16 . The use of a combination according to  claim 1 , for the manufacture of a medicament for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephrits, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke.  
   
   
       17 . The use of a combination according to  claim 1 , for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non- diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke.